Infection Treatment – Antibiotic Selection

Life-threatening Infections

Sepsis and other severe infections mean that a serious infection affects the entire body, causing damage to vital organs such as the heart, lungs, brain, and kidneys, which may stop functioning properly. Sometimes, even a mild infection can quickly develop into a critical condition that leads to multi-organ failure. The affected person often feels very ill and finds it difficult to manage independently. Symptoms often appear suddenly, sometimes within a few hours. In relevant cases, investigation and identification of the infection focus with surgical intervention (incision, drainage, excision, amputation, debridement, decompression, etc.) when possible are done promptly, striving for “Source control” along with appropriate antibiotic treatment. Antibiotic therapy is the cornerstone of treating severe infections, a common condition among ICU patients. Collecting relevant cultures (respiratory secretions, wound culture, urine culture, blood cultures, CSF) before antibiotic treatment is crucial but should not delay the initiation of antibiotics in life-threatening infections. In septic shock, always administer an extra loading dose of β-lactam antibiotics (cefotaxime, pip/taz, or meropenem) approximately 3 hours after the first dose. Serious and complicated infections should be evaluated by an infectious diseases consultant within 24 hours or no later than the next business day.

Addition of aminoglycoside (AG) should be considered in septic shock if the infection is suspected to be caused by G-neg bacteria (unknown focus, urosepsis, abdominal infection) and other β-lactam antibiotics than meropenem are being used.

Contraindications for aminoglycosides: chronic/(acute) renal failure, hearing impairment. Tobramycin (Nebcina©) is dosed at 7 mg/kg x 1. For increased risk of ESBL bacteria (previous ESBL infection, care/stay in ESBL-endemic countries in the last 3 months), amikacin (ESBL bacteria often resistant to tobramycin) is given instead. Amikacin (Biklin©) is dosed at 25 mg/kg x 1. If BMI >30, AG is dosed based on “adjusted body weight” (ABW) according to the formula: ABW = IBW + 0.4 x (TBW-IBW). Usually, one dose of AG is sufficient, but further dosing is guided by concentration determination after 24 hours (trough level).

Additional treatment with vancomycin should be considered for known MRSA carriage (not for urinary focus) and suspected CVK-related coagulase-negative staphylococci infection. Loading dose: 30 mg/kg (max 2 g), followed by 15 mg/kg x 3 (lower dose in established renal failure – consult infectious diseases). Trough level determination before the 4th dose. Vancomycin can also be administered as a continuous infusion.

Echinocandin (caspofungin, micafungin, anidulafungin) should be considered in the presence of risk factors for invasive fungal infection.

Renal failure/dialysis: Give the initial dose of β-lactam antibiotics, as well as an extra loading dose (3 hours) in septic shock, as with normal kidney function.

Common Severe Infections:

• Abdominal infections
• Intestinal infections
• CNS infections
• Endocarditis
• Gynecological infections
• Skin and soft tissue infections
• Joint and bone infections
• Lower respiratory tract infections (influenza, Covid-19, pneumonia, COPD exacerbations, chronic bronchitis)
• Neutropenic fever
• Suspected infection without sepsis/septic shock
• Sepsis and septic shock
• STIs (rarely cause systemic symptoms)
• Urinary tract infections (cystitis, pyelonephritis, pyelitis)
• Thoracic abscesses

Common Symptoms of Severe Infections:

• Fever
• Chills
• Difficulty breathing, dyspnea, tachypnea
• Confusion, altered consciousness, somnolence
• Diarrhea or vomiting
• Severe abdominal pain, or pain in the back, muscles, or joints
• Muscle weakness (especially in older individuals)
• Possible localized swelling, redness, and pain in soft tissue infections

Not all symptoms may be present, but the more symptoms, the higher the likelihood of sepsis. Fever is common, but not everyone will have it.

*For severe sepsis, add Nebcina during the first day at a dose of 5-7 mg/kg×1 if Creatinine clearance >80; 4.5-2.2 mg/kg×1 if Creatinine clearance 80-41; 2.2-1 mg/kg×1 if Creatinine clearance 40-20; weight ~ lean body mass. Serum concentration of tobramycin, administered once daily, is measured 8 hours after the dose and should be 1.5-4.0 mg/L at that time.

Classification of bacteria

Sepsis and Septic Shock

Background

Sepsis means that an infection affects the entire body, causing vital organs such as the heart, lungs, brain, and kidneys to malfunction. Even a mild infection can develop into a serious or life-threatening condition. Those affected usually feel very ill and struggle to manage independently. Symptoms often appear suddenly in sepsis, sometimes within a few hours.

Common Symptoms of Sepsis

• Chills
• Fever
• Difficulty breathing, dyspnea, tachypnea
• Confusion
• Diarrhea or vomiting
• Severe abdominal pain, or pain in the back, muscles, or joints
• Muscle weakness (especially in older individuals)

Not all symptoms may be present, but the more symptoms, the higher the likelihood of sepsis. Fever is common, but not everyone will have it.

Definition of Sepsis

Sepsis is defined as an infection that triggers a systemic response in the form of:

• Fever/hypothermia >38°C or < 36°C
• Tachycardia > 90 beats per minute
• Increased respiratory rate >20 breaths per minute
• Leukocytes >12 x10⁹/L or <4 x10⁹/L

Early identification and proper treatment of patients with severe sepsis (blood poisoning) reduces mortality. Severe sepsis can affect anyone, but infants and the elderly are at increased risk, as are people with chronic diseases or weakened immune systems. Reliable prevalence data is lacking in Sweden, but it is estimated that 100–300 people per 100,000 inhabitants are affected each year. Mortality in previous studies was reported as very high, with 20% for severe sepsis and 45% for septic shock. Recent studies indicate a mortality rate of around 15-20%. Severe sepsis is one of the most lethal conditions in emergency departments. According to international and national recommendations, patients with severe sepsis should receive proper antibiotic treatment within one hour of arriving at the hospital. Research has shown that early treatment with antibiotics, intravenous fluids, oxygen, and supportive therapy is crucial in severe sepsis. Inadequate initial antibiotic therapy in severe sepsis with a positive blood culture doubles mortality. Delayed appropriate antibiotic treatment in septic shock increases mortality by nearly 8 percentage points per hour during the first 6 hours. The more organ systems fail and the higher the initial lactate level, the higher the mortality rate. This care program describes a sepsis chain for the acute care of patients with or suspected of having severe sepsis and septic shock. The goal is early identification of patients with infections at risk of developing severe sepsis. As part of the sepsis chain, support for management in prehospital, emergency, and correct care placement has been developed. The care chain is supported by cooperation between different parts of healthcare, with a focus on early identification and treatment without delay.

When two or more of the above factors are present, the patient meets the criteria for sepsis. However, what we commonly refer to as “sepsis” is actually severe sepsis and septic shock, meaning the infection has caused hypotension, hypoperfusion, and/or organ dysfunction.

The Swedish Infectious Diseases Association has developed guidelines for the assessment of severe sepsis and septic shock as described below. The changes must be caused by the systemic reaction and not be a direct effect of local infection. The changes must be new and not caused by another underlying disease. For the definition of severe sepsis to be met, the patient must have sepsis as defined above, and one or more of the following criteria must be present:

Hypotension

• Systolic blood pressure <90 mm Hg

Organ Dysfunction

• Altered mental status; new-onset confusion, restlessness, aggression, or somnolence
• Renal impairment; creatinine increase >45 μmol/L or oliguria, urine output < 0.5 ml/kg for at least 2 hours despite adequate fluid administration lung impairment:
• pO₂ <7.0 kPa on room air (SO₂ approximately <86%), pO₂ <5.6 kPa on room air (SO₂ approximately <78%) if the lungs are the focus of infection
• Coagulopathy; petechiae, ecchymoses, INR >1.5, a-APT time >60 s, or PLT < 100
• Liver dysfunction; s-bilirubin > 45 μmol/L.*

Hypoperfusion

• Lactate >1 mmol above the upper reference limit, or BE ≤-5 mmol/L
• Decreased capillary refill, cold clammy skin, mottling.

*Intestinal impairment (absence of bowel sounds) is considered organ dysfunction in international guidelines, but not in the guidelines of the Swedish Infectious Diseases Association.

The often rapid and unpredictable progression of severe sepsis highlights the importance of clear routines for monitoring vital signs and set thresholds for physician contact and ICU care. It is especially during the first 24 hours after sepsis onset that patients are at risk of deterioration, which justifies enhanced monitoring and readiness to act during this period to prevent the development of:

• Progressing severe sepsis: Worsening of vital signs or rising lactate during the observation period.
• Septic shock: Sepsis with hypotension despite adequate fluid therapy.

Epidemiology

Severe sepsis can affect anyone, but infants and the elderly are at higher risk, as well as people with chronic illnesses or weakened immune systems. Accurate prevalence data is lacking in Sweden, but it is estimated that 100-300 people per 100,000 inhabitants are affected each year.

Preventive Treatment

Appropriate treatment of infections requiring antibiotics without unnecessary delay is important to prevent progression to severe sepsis. The work with STRAMA guidelines is a good tool for outpatient doctors to prescribe antibiotics based on proper indications. Overuse of antibiotics risks creating conditions for the development of antibiotic resistance, which can negatively affect outcomes in severe sepsis. For more information on STRAMA’s guidelines for outpatient care; link

General vaccination programs are crucial in preventing certain severe infectious diseases. Annual influenza vaccination for at-risk groups is particularly important to prevent secondary cases of sepsis, as well as pneumococcal vaccination according to given recommendations. Immunocompromised patients are particularly vulnerable, and it is therefore important that these patients, in case of infection complications, see a doctor with the right expertise to assess the sometimes subtle symptoms that may precede or indicate a serious infection. Furthermore, it is essential to inform patients undergoing immunosuppressive treatment on how to act at the first signs of infection. In some cases, special vaccination may be indicated for immunosuppression.

Symptoms, Clinical Findings, and Early Identification

Severe sepsis is a serious infection characterized by organ damage. Most patients with community-acquired severe sepsis and septic shock are classified as red or orange according to the emergency department’s triage system (RETTS) upon arrival at the emergency department. However, the initial presentation can sometimes be difficult to interpret, and a range of symptoms and clinical findings may occur, which can vary depending on the site of infection, infecting agent, and the patient’s age and comorbidity.

Patients with severe sepsis or septic shock often have a fever or a history of fever and one of the following; elevated heart rate >90/min, elevated respiratory rate >20/min, falling blood pressure, low oxygen saturation <90%, restlessness and confusion, gastrointestinal symptoms such as abdominal pain, diarrhea, or vomiting. With typical symptoms and acute onset with chills, high fever, and general malaise, it is easy to suspect severe sepsis, but many patients, especially the elderly, often present a more atypical picture with, for example, confusion as the only symptom of severe sepsis. It is important to always keep sepsis in mind when examining a critically ill patient with an unclear diagnosis.

Consider the following warning signs of severe infection:

V-BAS; Alertness/Blood Pressure/Respiratory Rate/Saturation or the 90/30/90 Rule:

• Alertness; reduced/new mental impairment
• Systolic blood pressure <90 mmHg
• Respiratory rate >30 breaths per minute
• Oxygen saturation <90%

Sepsis Alarm

For early identification, sepsis alarms should be used, which involve a modified version of RETTS focusing on patients at risk of serious infection. RETTS (Rapid Emergency Triage and Treatment System) is the triage system used in many emergency departments across the country. RETTS is based on vital signs (blood pressure, pulse, respiratory rate, alertness, and temperature) with specified thresholds to sort patients into the correct priority group. Red RETTS means that the patient’s oxygen saturation is below 90% despite oxygen treatment, respiratory rate is over 30 or under 8, blood pressure <90 mm Hg, pulse >130, or that the patient is having seizures or is unconscious.

In addition to vital signs, an ESS (Emergency Signs and Symptoms) should be added. For severe sepsis, ESS 47 (infection, fever, local infection) is applied. ESS 51 should also be applied (known adrenal insufficiency, immunodeficiency, or immunosuppression), which finally determines the patient’s priority.

A sepsis alarm is triggered in patients with red RETTS who have a fever or a history of fever. In these cases, the patient is triaged according to a special algorithm, and an infectious disease specialist/emergency physician is called to the emergency room immediately upon the patient’s arrival.

By focusing early on patients who have or are at risk of severe sepsis, it is ensured that the patient receives appropriate antibiotics within 60 minutes after blood cultures (2+2) are taken, and that correct supportive treatment is initiated and continues with intravenous fluids and oxygen.

SOME POINTS TO KEEP IN MIND TO AVOID MISSING PATIENTS WITH SEVERE SEPSIS

• Fever (>38.0°C) is not always present, and ear thermometers are unreliable. Hypothermia (<36.0°C) can be a serious sign in severe sepsis.
• “Found on the floor” may be secondary to sepsis
• Sepsis-induced confusion can be mistaken for a stroke.
• Remember that gastrointestinal symptoms and flu-like conditions may be due to severe sepsis.
• CRP may be normal or only moderately elevated initially.
• Check the skin – petechiae? Infected wounds?
• Consider reduced immune response in certain groups such as patients with rheumatic systemic diseases, IBD, malignant tumors, transplanted patients, splenectomized patients, and patients on current or recent treatment with immunomodulating drugs such as Prednisolone 15 mg or more, Methotrexate®, Remicade® (infliximab), Enbrel® (etanercept), cytostatics, and others.

Primary Measures

• Monitoring – follow blood pressure, pulse, oxygen saturation, alert
  
  ness!
• Establish peripheral intravenous access.
• Oxygen 2–5 liters via nasal cannula, >5 liters via mask, target saturation >93%. Use caution with COPD! Inform the emergency department if the patient has COPD.
• Infusion of Ringer’s acetate, if BP <90 mm Hg, administer a bolus dose of 500–1,000 ml over 30 minutes, repeat until treatment goal is reached, i.e., BP >90 mm Hg. In total, at least 30 ml/kg IV should be given within 3 hours in severe sepsis with hypotension.
• Paracetamol should only be given if the patient is clinically affected by the fever or in cases of ongoing cerebral ischemia/seizure/cardiac ischemia.

PREHOSPITAL IDENTIFICATION AND MANAGEMENT

• Suspected infection is generally identified using RETTS
• Vital signs should also include ESS 47, which determines the patient’s priority. In some cases, ESS 51 (known adrenal insufficiency, immunodeficiency, or immunosuppression) should be used.
• In addition to this analysis, note the following criteria as signs of suspected severe infection:

Fever (temp >38.0°C) or low temp (<36.0°C)/history of fever and any of the following symptoms/signs:

• Petechiae/rash
• Signs of infected skin/soft tissue/joints
• New onset of severe pain
• Cerebral impairment/severe headache
• Urinary symptoms (especially with an indwelling catheter)
• Central venous catheter or other invasive port with signs of infection

Epidemiology? Always ask about recent travel abroad!

Remember that fever may be absent in immunocompromised patients and in patients who have taken paracetamol and NSAIDs, and that diarrhea/abdominal pain/vomiting are common symptoms of severe sepsis.

• Oxygen, adjusted according to saturation, 2–5 liters via nasal cannula, >5 liters via mask, target saturation >93%. Use caution with COPD! Inform the emergency department if the patient has COPD.
• Establish peripheral intravenous access.
• Consider intraosseous access if there is difficulty with IV access in critically ill patients who urgently need access for fluid/medication administration.
• Infusion of Ringer’s acetate, if BP <90 mm Hg, administer a bolus dose of 500–1,000 ml over 30 minutes, repeat until treatment goal is reached, i.e., BP >90 mm Hg. In total, at least 30 ml/kg IV should be given within 3 hours in severe sepsis with hypotension.
• Avoid the general prescription of paracetamol for fever. Antipyretics should only be given if the patient is clinically affected by the fever or in cases of ongoing cerebral ischemia/seizure/cardiac ischemia.

Intrahospital Diagnosis and Treatment

• Initial management according to A – B – C – D – E
• Peripheral intravenous access x 2
• Consider central venous catheter (CVC) or intraosseous access if difficulty with IV access in critically ill patients urgently needing access for fluid/medication administration.
• Blood cultures 2+2
• Arterial or venous blood gas for lactate analysis.
• Blood tests; CRP, white blood cell count, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), liver function tests, urine dipstick, blood glucose.
• Urine culture (if needed, catheterization) and other relevant cultures as per doctor’s orders.
• Is there a suspected bacterial infection? Assess the infection focus. After appropriate cultures, consider antibiotics as per point 15.
• If meningitis is suspected, perform lumbar puncture (LP); see national guidelines at www.infektion.net
• ECG
• Consider chest X-ray bedside.
• Vital signs every 5 minutes initially until the patient is stabilized.
• Epidemiology? Always ask about recent travel abroad!
• Remember that fever may be absent in immunocompromised patients and in patients who have taken paracetamol and NSAIDs, and that diarrhea/abdominal pain/vomiting are common symptoms of severe sepsis.

Treatment

• The infectious disease specialist/emergency doctor* joins the emergency room during a sepsis alarm. If there is no infectious disease specialist available at the hospital, contact the specialist by phone for advice on investigation and antibiotic selection, especially for immunocompromised patients or those suspected of carrying resistant bacteria.
• Oxygen, adjusted according to saturation, 1–5 liters via nasal cannula, >5 liters via mask, treatment goal >93%. Use caution with COPD!
• Infusion of Ringer’s acetate, if BP <90 mm Hg, administer a bolus dose of 500–1,000 ml over 30 minutes, repeat until treatment goal BP >90 mm Hg is reached. In total, at least 30 ml/kg IV should be given within 3 hours in severe sepsis with hypotension or lactate >4.
• Choice of antibiotics is based on the severity of the infection and the suspected focus.

If antibiotics are prescribed, they should be administered without delay in the emergency department!

• Consider invasive management of the infection focus (so-called source control) in cases such as septic arthritis, abscess, obstructive pyelonephritis, empyema, bowel perforation, gynecological infection, or necrotizing fasciitis.
• If the patient is on or has recently finished treatment with corticosteroids, administer Solu-Cortef 100 mg IV.
• Insert a urinary catheter and attach a bag for monitoring urine output, target 0.5 ml/kg/hour.
• Administer Albumin 20% 100 ml if hypotension persists after 2–3 liters of Ringer’s acetate. Do not use starch solutions (e.g., Voluven). If Albumin is not available, continue with Ringer’s acetate.
• Avoid the general prescription of paracetamol for fever. Antipyretics should only be given if the patient is clinically affected by the fever or in cases of ongoing cerebral ischemia/seizure/cardiac ischemia.

*Which doctor is called depends on the respective hospital; if an infectious disease specialist is available, they should be called. Otherwise, the medical or emergency doctor should be contacted according to local guidelines.

Care Level – Admission

• Decision on the level of care: ICU/intermediate care or general ward.
• Transfer to the infectious disease ward, emergency care ward, or another ward with sufficient monitoring resources without delay. While waiting for transfer, check vital parameters every 15 minutes.
• Evaluate if treatment limitations are necessary.

The Emergency Room – Continued Deterioration of Vital Functions After Initial Measures

Establish contact with the Medical Emergency Team (MET) or ICU consultant (infectious disease consultant) to assess the need for ICU care.

• If BP <90 despite IV fluids or saturation <90 despite oxygen therapy
• If lactate >4 or increasing
• If respiratory rate >30 despite treatment
• In cases of severe organ dysfunction such as reduced consciousness

Diagnostics

• Peripheral IV access x2
• Blood culture 2+2
• Arterial or venous blood gas for lactate analysis, if >3.5 the patient should be upgraded to red RETTS and a sepsis alarm should be triggered, see above.
• Blood tests: CRP, leukocytes, platelets, prothrombin time (PT), activated partial thromboplastin time (APTT), liver function tests, urine dipstick, blood glucose
• Urine culture (with catheter if needed) and other relevant cultures as per the doctor’s orders.
• Is there a suspected bacterial infection? Evaluate the infection focus. After appropriate cultures, decide on antibiotics as per point 15.
• If meningitis is suspected, perform a lumbar puncture (LP), see national guidelines at www.infektion.net
• Vital parameters and monitoring at 15-minute intervals.
• Epidemiology? Always ask about recent travel abroad!
• Remember that fever may be absent in immunocompromised patients and in patients who have taken paracetamol and NSAIDs, and that diarrhea/abdominal pain/vomiting are common symptoms of severe sepsis.

Treatment

• During the day, primarily handled by the infectious disease day consultant*, during on-call hours consult the infectious disease consultant by phone, who will assess the patient in the emergency room if necessary, especially for immunocompromised patients and those known to carry resistant bacteria.
• Oxygen, adjusted according to saturation, 1–5 liters via nasal cannula, >5 liters via mask, target saturation >93%. Use caution with COPD!
• Infusion of Ringer’s acetate 1,000 ml, a total of at least 30 ml/kg IV should be given within 3 hours in severe sepsis with hypotension or lactate >4.
• Antibiotic choice is based on the severity of the infection and the suspected focus.

If antibiotics are prescribed, they should be administered without delay in the emergency room!

• Consider invasive management of the infection focus (so-called source control) in cases such as septic arthritis, abscess, obstructive pyelonephritis, empyema, bowel perforation, gynecological infection, or necrotizing fasciitis.
• If the patient is on or has recently finished treatment with corticosteroids, administer Solu-Cortef 100 mg IV.
• Antipyretics should only be given if the patient is clinically affected by the fever or in cases of ongoing cerebral ischemia/seizure/cardiac ischemia. Avoid general prescriptions for fever.

*Which consultant is called depends on the respective hospital. Where available, an infectious disease consultant should be contacted. Otherwise, consult the medical or emergency consultant according to local guidelines.

Antibiotic Treatment in the Intensive Care Unit

Note: Always take cultures from relevant locations before starting antibiotic treatment, such as blood, sputum, wound, and urine.

In cases of severe sepsis, add Nebcina during the first 24 hours at a dose of 5-7 mg/kg×1 if creatinine clearance >80; 4.5-2.2 mg/kg×1 if creatinine clearance 80-41; 2.2-1 mg/kg×1 if creatinine clearance 40-20; weight ~ lean body mass. Tobramycin serum concentration, administered once daily, is measured 8 hours after the dose and should be 1.5-4.0 mg/L at that time.

The dosing instructions assume an adult patient with normal kidney function. Creatinine clearance (ml/min) = F x (140-age) x weight/S-creatinine; F≈1.2 for men; F≈1.0 for women.

In cases of increased risk for ESBL-producing gut bacteria (foreign travel, foreign hospital care, known colonization): Meropenem 1g x 4 + amikacin (Biklin) 20-25 mg/kg x 1. In cases of fasciitis/myositis, consult the infectious disease specialist for consideration of IV immunoglobulin. For meningitis, always add dexamethasone (Betapred) 8 mg x 4.

Higher doses and more frequent dosing are required for severe sepsis/septic shock due to increased distribution volume and impaired microcirculation. Usually, lower/less frequent dosing is needed later in the course. Add Nebcina 1 dose/day for severe sepsis/septic shock. Normal dose 7 mg/kg. Lower dose (5 mg/kg) in older patients or those with chronic kidney disease. Avoid Nebcina if GFR <20 ml/min. For treatment with Biklin, take trough concentration just before the next dose.

Antibiotic Choice in Severe Sepsis

Severe sepsis and septic shock are very serious conditions that require early, correct treatment. It is important to start with broad-spectrum antibiotic therapy.

Check for previous colonization with resistant bacteria and review the microbiology domain, also evaluate local resistance patterns.

Contact the infectious disease consultant when managing patients with progressing severe sepsis and septic shock, especially when the infection is suspected to be caused by resistant bacteria or in immunocompromised patients . The following antibiotic dosing applies to initial management; continued dosing and antibiotic treatment in cases of persistent severe sepsis or septic shock should be discussed with the infectious disease consultant.

The following antibiotic suggestions apply only in cases of severe sepsis and septic shock. For correct treatment, see previous definitions on p. 6. Aim for targeted treatment if the infection focus is suspected. Generally, higher initial antibiotic doses and more frequent dosing (an extra dose after 4 hours, the next dose 4 hours later, when treating with beta-lactam antibiotics such as Benzylpenicillin, Cefotaxime, Piperacillin/Tazobactam, and Meropenem/Imipenem) are recommended in severe sepsis/septic shock as the distribution volume in these conditions is increased, leading to low tissue concentrations with standard dosing. When stabilized, normal dosing applies. For more detailed information, see the national care program at www.infektion.net.

ANTIBIOTIC CHOICE FOR PATIENTS WITH SEVERE SEPSIS OR SEPTIC SHOCK**

* Use the higher dose of aminoglycosides in cases of progressing severe sepsis and septic shock. In milder cases of severe sepsis that respond well to initial fluid therapy, aminoglycosides can be withheld.

** If current or previous colonization with ESBL-producing pathogens is suspected, Meropenem/Imipenem 1g should be administered initially. If risk factors for infection caused by ESBL-producing pathogens, such as a history of travel to regions with a high prevalence of antibiotic resistance or residence in a nursing home with a high prevalence of resistant bacteria, consult an infectious disease specialist.

ANTIBIOTIC CHOICE IN PREGNANT PATIENTS WITH SEVERE SEPSIS OR SEPTIC SHOCK

Penicillins, cephalosporins, carbapenems, and clindamycin are safe to administer. A single dose of aminoglycosides can be considered if the indication is strong. Consult an infectious disease specialist. Avoid quinolones throughout pregnancy, and avoid macrolides during the first trimester (doxycycline can be given in the first trimester but should be avoided in the second and third trimesters), see www.infpreg.se.

ANTIBIOTIC CHOICE IN PATIENTS WITH RENAL FAILURE AND SEVERE SEPSIS OR SEPTIC SHOCK

Renal failure is very common in severe sepsis and septic shock. In principle, the first dose can always be given as a full dose, but subsequent doses must be adjusted according to kidney function.

ANTIBIOTIC CHOICE IN SEVERELY OBESE PATIENTS WITH SEVERE SEPSIS OR SEPTIC SHOCK

There is uncertainty regarding optimal antibiotic doses in severely overweight/obese patients. The Swedish Infectious Disease Association recommends adjusting the dose of certain antibiotics for patients with a BMI >30 kg/m² (BMI=weight/height²). Consult an infectious disease specialist for advice.

ANTIBIOTIC CHOICE IN PATIENTS WITH SEPSIS WITHOUT ORGAN DYSFUNCTION (FEBRILE BACTERIAL INFECTION)

Other Treatments in Severe Sepsis

• DVT prophylaxis: Low molecular weight heparin and compression stockings should be given to all patients with severe sepsis unless there is a risk of bleeding or other contraindications.
• PPI: If PT >1.5 or platelets <50 or hypotension is present, PPI (proton pump inhibitor) is given as ulcer prophylaxis, Nexium 40 mg x 1 IV. The treatment should be discontinued when the patient is stabilized and able to eat per os.
• Blood glucose control: Aim for glucose levels <10 mmol/L.

Ethical Considerations in Severe Sepsis

The care program is a support for initial management, and it is essential that ethical principles, the prognosis of any underlying chronic diseases, and the prognosis of the acute illness are considered. Each patient should be assessed individually regarding appropriate care interventions and care level. Deviations from treatment should be justified and documented.

In the group of elderly patients with multiple illnesses, it is not uncommon for the patient to, after careful consideration, decline acute hospital care. In such cases, treatment at home with support from a mobile elderly care team can be arranged where possible. If this care is unavailable, the care should be adapted as best as possible given the circumstances.

Follow-up

Proper monitoring while awaiting a hospital bed and evaluation of treatment effectiveness through lactate level checks and vital parameters in accordance with the patient’s RETTS score.

A reasonable treatment goal is for the patient to have a systolic blood pressure >90 mmHg and oxygen saturation >93% (not applicable to COPD patients) within 1 hour of treatment initiation. Within 6 hours, urine output should be adequate >0.5 ml/kg/hour, and any elevated lactate value should have decreased. After 3–6 hours, the responsible physician should assess whether the patient has met the treatment goals. The risk of rapid deterioration is highest during the first 24 hours in the hospital. If vital parameters are deteriorating, NEWS >6, contact the Medical Emergency Team (MET) and the infectious disease consultant by phone.*

Before the patient leaves the emergency department, a NEWS assessment should be performed, and upon arrival at the ward, a NEWS assessment should be repeated. During handover to the ward, clear levels for ongoing fluid treatment, oxygen therapy, target levels for oxygen saturation and blood pressure, as well as when the next antibiotic dose should be given and in what dose, along with intervals for NEWS assessments, should be communicated.

*Which consultant is called depends on the respective hospital. If an infectious disease consultant is available, they should be contacted. Otherwise, contact the medical or emergency consultant according to local guidelines.

• Surviving Sepsis Campaign, via the link http://www.survivingsepsis.org
• Infectious Disease Society’s care program, version 2013 via the link www.infektion.net
• Glickman et al 2010, Acad Emerg Med. 2010 Apr;17(4):383-90. doi: 10.1111/j.1553-2712.2010.00664
• Widgren B et al. The Journal of Emergency Medicine, 2011;40:623-628.

Bacterial Sensitivity to Various Antibiotics

The tables above show bacterial sensitivity to various antibiotics. Published with permission from UAS. The images are clickable for a more detailed view in higher resolution. Different colors indicate classes of antibiotics.

Classification of Bacteria by Cocci/Rods, G +/-, Aerobic/Anaerobic

Antibiotics for Reduced Renal Function

Parenteral Antibiotics for Children

Fungal Infections in Intensive Care

Fungal infections and fungal sepsis are common in intensive care, especially in patients receiving prolonged treatment with broad-spectrum antibiotics, immunocompromised patients, those in poor nutritional status, or those with extensive necrosis or burns. Antifungal agents are often added to the treatment of ICU patients. The presence of deep fungal infection can be confirmed with beta-glucan testing. Beta-glucan is a fungal antigen that can be detected in the blood in cases of invasive fungal infection. Values above 100 pg/mL are considered positive, while values below 100 pg/mL are negative. However, beta-glucan does not detect mucormycosis, cryptococcus, or blastomyces. Treatment for invasive fungal infections typically needs to continue for an extended period. The recommended treatment duration is at least 2 weeks after the first negative test. In some cases, treatment is required for 1-3 months.

Here are some simple memory rules for antifungal treatment in invasive fungal infection.

• Fluconazole (Diflucan, Fluconazole) – for the treatment of candida albicans infections

Dosage: 800 mg on day 1. Maintenance dose: 400 mg once daily

• Cancidas (caspofungin) – for candida glabrata or resistance to Fluconazole

Dosage: A 70 mg single loading dose should be administered on day 1, followed by 50 mg daily. For patients weighing more than 80 kg, after the initial 70 mg loading dose, 70 mg daily is recommended.

• Vfend (voriconazole) – for invasive aspergillosis

Dosage: Loading dose: 400 mg every 12 hours on the first day, then 200 mg every 12 hours

• Mycamine (micafungin) – like Cancidas: invasive candidiasis

Dosage: 100 mg/day

• Noxafil (posaconazole) – given orally/parenterally. Invasive aspergillus infection.

Dosage: 300 mg x 2 on day 1. Maintenance dose: 300 mg once daily

• Ecalta (anidulafungin) – primarily for liver or kidney failure. Invasive candidiasis.

Dosage: A starting dose of 200 mg should be given on day 1, followed by 100 mg per day thereafter.

• Cresemba (isavuconazonium) – invasive aspergillosis, mucormycosis.

Dosage: 200 mg x 3 should be given on days 1-2, followed by 200 mg per day thereafter.

• AmBisome (Amphotericin B) – severe systemic and deep fungal infections.

AmBisome liposomal should be administered as an intravenous infusion over 30-60 minutes. Start treatment with 3 to 5 mg/kg, administered daily for at least 14 days.